Malignant cells are characterized by the extracellular production of superoxide anions by membranous NADPH oxidase (NOX-1). Here, the activity of NOX is controlled by oncogenes such as e.g., RAS by involving RAC. The superoxide anions generated by malignant cells and their dismutation product hydrogen peroxide are essential for the proliferation of these cells and for the maintenance of their transformed state (Heinzelmann and Bauer, Biol. Chem., Vol. 391, 2010, p. 675-693).
However, the other side of the coin from the extracellular production of reactive oxygen species (ROS) is the formation of intercellular ROS-mediated signal paths selectively directing themselves against cells with the transformed phenotype. These are the main paths shown in FIG. 1, namely the HOCl and the NO/peroxynitrite signal path as well as two further paths of secondary importance, namely the nitryl chloride path and the metal catalyzed Haber-Weiss reaction that are not considered in the illustration. In the course of the tumor progression tumor cells acquire resistance against the intercellular ROS signal paths by expressing catalase on their cell membrane. This inhibits the HOCl and the nitryl chloride path as well as the metal catalyzed Haber-Weiss reaction by converting hydrogen peroxide into water and oxygen, and counteracts the NO/peroxynitrite path by decomposing peroxynitrite and oxidizing NO to NO2 with the help of its active intermediate compound I, and so prevents the formation of peroxynitrite.
Abolishing the catalase-mediated protection of tumor cells represents an attractive concept for the development of a novel form of tumor therapy that is specifically directed against cells with the malignant phenotype (due to the features of membranous catalase and superoxide anion production) and does not endangers normal cells, since these neither produce extracellular superoxide anions nor express membranous catalase.